Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer

Annette Hasenburg, Xiao Wen Tong, Augusto Rojas-Martinez, Cassandra Nyberg-Hoffman, Christina C. Kieback, Alan L. Kaplan, Raymond H. Kaufman, Ibrahim Ramzy, Estuardo Aguilar-Cordova, Dirk G. Kieback

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Introduction: Patients with recurrent ovarian cancer were treated with a replication-deficient recombinant adenovirus containing the herpes simplex virus thymidine kinase gene administered intraperitoneally (i.p.) followed by administration of an anti-herpetic prodrug and topotecan. Materials and Methods: A total of 10 patients with stage IIIc epithelial ovarian cancer underwent secondary debulking to ≤0.5 cm residual tumor. Patients with normal i.p. flow received i.p. delivery of adenovirus. Two patients each were treated on dose level 1 (2 x 1010 vector particles (VP)), dose level 2 (2 x 1011 VP), and dose level 3 (2 x 1012 VP); four patients were treated on dose level 4 (2 x 1013 VP). Acyclovir and topotecan were started 24 hours after vector delivery. Results: No patient treated at any dose level incurred unanticipated toxic effects, and all side effects resolved. The most common adverse event was myelosuppression: grade 3 or 4 thrombocytopenia with grade 2-4 anemia in three patients and grade 3 or 4 neutropenia in eight patients. Three patients developed thrombocytosis and three patients had a mild elevation of serum glutamic pyruvic transaminase/alanine aminotransferase. Temperature elevations that were not associated with detectable infection occurred in two patients. Discussion: l.p. delivery of adenoviral vector with concomitant topotecan chemotherapy was well tolerated without significant lasting toxicities. Side effects were independent of the dose of adenoviral vector.

Original languageEnglish (US)
Pages (from-to)839-844
Number of pages6
JournalCancer Gene Therapy
Volume7
Issue number6
DOIs
StatePublished - 2000

Keywords

  • Acyclovir
  • Gene therapy
  • Intraperitoneal therapy
  • Ovarian cancer
  • Thymidine kinase
  • Topotecan

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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